Antiviral potency of long-acting islatravir subdermal implant in SHIV-infected macaques

Fernanda P. Pons-Faudoa, Nicola Di Trani, Simone Capuani, Ilaria Facchi, Anthony M. Wood, Bharti Nehete, Ashley DeLise, Suman Sharma, Kathryn A. Shelton, Lane R. Bushman, Corrine Ying Xuan Chua, Michael M. Ittmann, Jason T. Kimata, Peter L. Anderson, Pramod N. Nehete, Roberto C. Arduino, Alessandro Grattoni

Research output: Contribution to journalArticlepeer-review

Abstract

Treatment nonadherence is a pressing issue in people living with HIV (PLWH), as they require lifelong therapy to maintain viral suppression. Poor adherence leads to antiretroviral (ARV) resistance, transmission to others, AIDS progression, and increased morbidity and mortality. Long-acting (LA) ARV therapy is a promising strategy to combat the clinical drawback of user-dependent dosing. Islatravir (ISL) is a promising candidate for HIV treatment given its long half-life and high potency. Here we show constant ISL release from a subdermal LA nanofluidic implant achieves viral load reduction in SHIV-infected macaques. Specifically, a mean delivery dosage of 0.21 ± 0.07 mg/kg/day yielded a mean viral load reduction of −2.30 ± 0.53 log10 copies/mL at week 2, compared to baseline. The antiviral potency of the ISL delivered from the nanofluidic implant was higher than oral ISL dosed either daily or weekly. At week 3, viral resistance to ISL emerged in 2 out of 8 macaques, attributable to M184V mutation, supporting the need of combining ISL with other ARV for HIV treatment. The ISL implant produced moderate reactivity in the surrounding tissue, indicating tolerability. Overall, we present the ISL subdermal implant as a promising approach for LA ARV treatment in PLWH.

Original languageEnglish (US)
Pages (from-to)18-27
Number of pages10
JournalJournal of Controlled Release
Volume366
Early online dateDec 29 2023
DOIs
StatePublished - Feb 2024

Keywords

  • Drug delivery
  • HIV treatment
  • Implantable devices
  • Islatravir
  • Refillable

ASJC Scopus subject areas

  • Pharmaceutical Science

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